Back to resultsValaciclovir Hydrochloride Phase III for Hematopoietic Stem Cell Transplantation Patients
Primary Purpose
Herpes Simplex
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
VACV tablets (Adults or pediatrics) or granules (pediatrics)
Sponsored by
About this trial
This is an interventional prevention trial for Herpes Simplex focused on measuring Herpes simplex infection, valaciclovir, herpes simplex virus, hematopoietic stem cell transplantation
Eligibility Criteria
Inclusion Criteria:
- Patients who are planning to undergo hematopoietic stem cell transplantation, except cord blood transplantation.
- Patients aged from 1 and above to under 65 at the time of informed consent.
- Patients who can submit their voluntary written informed consent if they are 12 years old and over.
- Patient is male or female. Male patients must be willing to use adequate contraception during the study. Female patients of childbearing potential must agree to consistently perform any of the contraceptive methods.
- QTc <450 msec, or QTc <480 msec in patients with bundle branch block. (values based on either single ECG values or triplicate ECG averaged QTc values)
- Liver test (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2x upper limit of normal (ULN); alkaline phosphatase (Al-P)and total bilirubin <=1.5xULN (total bilirubin >1.5xULN is acceptable if direct bilirubin <35%).
Exclusion Criteria:
- Patients with a history of HSCT.
- Patients who are judged to be in the following condition by the investigator (or subinvestigator): the clinical severity of malabsorption syndrome, vomiting, mucositis or other gastrointestinal dysfunction is so serious that orally administered VACV can not be absorbed.
- Patients who have known nucleoside analogs hypersensitivity.
- Patients who have a concurrent or past history of renal function disorder (serum creatinine >=1.5x ULN).
- Patients who have serious complication (eg, other malignant tumours, cardiac disorder, juvenile diabetes).
- Patients who are currently treated with the prohibited concomitant drugs.
- Patients with evidence of chronic hepatitis B or C.
- Patients with AIDS or patients infected with HIV.
- Patients who were given other trial products within 30 days before initiation of administration of this trial product or those who intend to participate in other clinical trials.
- Patients who are pregnant or probably pregnant.
- Patients who can not follow the protocol because of psychological, family, social or geological reasons.
- Patients are not allowed to participate in this clinical trial if the investigator (or subinvestigator) judges that their participation is inappropriate.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VACV (256U87; valaciclovir hydrochloride)
Arm Description
Adult patients (16-65 years): A VACV tablet (containing 500mg of valaciclovir) is orally given twice daily. Pediatric patients (1-16 years): VACV granules are orally given at a dose of 25 mg/kg b.w. twice daily. The maximum dose per treatment is limited to 500 mg. Pediatric patients weighing 40 kg or over may be orally given a VACV tablet (containing 500 mg of valaciclovir) twice daily.
Outcomes
Primary Outcome Measures
Number of Participants With a Herpes Simplex Virus (HSV) Infection
Viral isolation/identification was conducted if the investigator (or subinvestigator) suspected HSV infection according to the relevant clinical symptoms (oral mucositis, skin infection, genital herpes, and pneumonia). If the result of viral isolation/identification was positive, the participant concerned was defined as a case of HSV infection. For reference, a virus deoxyribonucleic acid (DNA) identification (PCR) was simultaneously performed.
Secondary Outcome Measures
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LD) Values at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of ALP, ALT, AST, CPK, GGT, and LD at Screening, Day 14, and Day 35.
Mean Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid Values at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of direct bilirubin, total bilirubin, creatinine, and uric acid at Screening, Day 14, and Day 35.
Mean Cholesterol, Chloride, Glucose, Potassium, Sodium, Triglyceride, and Urea/Blood Urea Nitrogen (BUN) Values at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of cholesterol, chloride, glucose, potassium, sodium, triglycerides, and urea/BUN at Screening, Day 14, and Day 35.
Mean Albumin and Total Protein Values at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of albumin and total protein at Screening, Day 14, and Day 35.
Mean Basophil, Eosinophil, Lymphocyte, Monocyte, and Total Neutrophil Values at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at Screening, Day 14, and Day 35.
Mean Platelet Count and White Blood Cell (WBC) Count at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of platelet count and WBC count at Screening, Day 14, and Day 35.
Mean Red Blood Cell Count at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of the red blood cell count at Screening, Day 14, and Day 35.
Mean Hemoglobin Values at Screening, Day 14, and Day 35
Blood samples were collected for the measurement of hemoglobin at Screening, Day 14, and Day 35.
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Screening, Day 14, and Day 35
Urinalysis parameters included: urine bilirubin (UB), urine occult blood (UOB), urine glucose (UG), urine ketones (UK), urine protein (UP), and urine urobilinogen (UUG). The dipstick is a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative (Neg), Trace, 1+, 2+, and 3+ (in order of increasing levels). Data are reported as the number of participants who had Neg, Trace, 1+, 2+, and 3+ levels at Screening, Day 14, and Day 35. If a category has not been reported for a specific parameter, then no participants were measured in that category.
Mean Urine Specific Gravity Values at Screening, Day 14, and Day 35
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Days 0, 7, 14, 21, and 35
Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Heart Rate at Days 0, 7, 14, 21, and 35
Heart rate is defined as the number of heartbeats per unit of time. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Screening and Day 35
The number of participants with normal, abnormal - clinically significant (CS), and abnormal - not clinically significant (NCS) ECG findings, as well as the number of participants with no results (NR), at Screening and Day 35 are presented. Findings were determined to be normal, abnormal CS, and NCS by the investigator.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01602562
Brief Title
Valaciclovir Hydrochloride Phase III for Hematopoietic Stem Cell Transplantation Patients
Official Title
A Multicenter, Open-label Study to Evaluate Preventive Efficacy for Herpes Simplex Virus Infection and Safety of 256U87 (Valaciclovir Hydrochloride) in Adult and Pediatric Hematopoietic Stem Cell Transplantation Patients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
May 7, 2012 (undefined)
Primary Completion Date
May 1, 2013 (Actual)
Study Completion Date
May 24, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the preventive efficacy for HSV infection and safety of valaciclovir (VACV) in the adult and pediatric HSCT patients.
Detailed Description
This clinical study is a multicenter open-label study on the adult and pediatric hematopoietic stem cell transplantation (HSCT) patients. The primary objective is to confirm the preventive efficacy for herpes simplex virus (HSV) infection of 256U87 (VACV: valaciclovir) due to the treatment before or immediately after hematopoietic stem cell transplantation. The secondary objective is to confirm the safety of VACV in the case of its use for such a purpose.
This clinical study consists of the following two periods: the screening period lasting 7 days at the longest and the administration period from 7 days before HSCT to 35 days after HSCT (43 days in total). During the administration period, adult patients are orally given a VACV tablet twice daily, while pediatric patients are orally given VACV granules twice daily at a dose of 25 mg/kg b.w. (maximum dose per treatment: 500 mg). Pediatric patients weighing 40 kg or over may be orally given a VACV tablet twice daily.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Herpes Simplex
Keywords
Herpes simplex infection, valaciclovir, herpes simplex virus, hematopoietic stem cell transplantation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VACV (256U87; valaciclovir hydrochloride)
Arm Type
Experimental
Arm Description
Adult patients (16-65 years): A VACV tablet (containing 500mg of valaciclovir) is orally given twice daily. Pediatric patients (1-16 years): VACV granules are orally given at a dose of 25 mg/kg b.w. twice daily. The maximum dose per treatment is limited to 500 mg. Pediatric patients weighing 40 kg or over may be orally given a VACV tablet (containing 500 mg of valaciclovir) twice daily.
Intervention Type
Drug
Intervention Name(s)
VACV tablets (Adults or pediatrics) or granules (pediatrics)
Other Intervention Name(s)
256U87 tablet or granule
Intervention Description
A white to slightly yellowish white film coated tablet contains 556 mg of valaciclovir hydrochloride (500 mg of valaciclovir)). VACV granules have no or slightly specific odor.
Primary Outcome Measure Information:
Title
Number of Participants With a Herpes Simplex Virus (HSV) Infection
Description
Viral isolation/identification was conducted if the investigator (or subinvestigator) suspected HSV infection according to the relevant clinical symptoms (oral mucositis, skin infection, genital herpes, and pneumonia). If the result of viral isolation/identification was positive, the participant concerned was defined as a case of HSV infection. For reference, a virus deoxyribonucleic acid (DNA) identification (PCR) was simultaneously performed.
Time Frame
From Day -7 (7 days before HSCT) to Day 35 (35 days after HSCT)
Secondary Outcome Measure Information:
Title
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Description
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame
From Day -7 (7 days before HSCT) to Day 35 (35 days after HSCT)
Title
Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LD) Values at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of ALP, ALT, AST, CPK, GGT, and LD at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid Values at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of direct bilirubin, total bilirubin, creatinine, and uric acid at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Cholesterol, Chloride, Glucose, Potassium, Sodium, Triglyceride, and Urea/Blood Urea Nitrogen (BUN) Values at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of cholesterol, chloride, glucose, potassium, sodium, triglycerides, and urea/BUN at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Albumin and Total Protein Values at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of albumin and total protein at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Basophil, Eosinophil, Lymphocyte, Monocyte, and Total Neutrophil Values at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Platelet Count and White Blood Cell (WBC) Count at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of platelet count and WBC count at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Red Blood Cell Count at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of the red blood cell count at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Mean Hemoglobin Values at Screening, Day 14, and Day 35
Description
Blood samples were collected for the measurement of hemoglobin at Screening, Day 14, and Day 35.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Screening, Day 14, and Day 35
Description
Urinalysis parameters included: urine bilirubin (UB), urine occult blood (UOB), urine glucose (UG), urine ketones (UK), urine protein (UP), and urine urobilinogen (UUG). The dipstick is a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative (Neg), Trace, 1+, 2+, and 3+ (in order of increasing levels). Data are reported as the number of participants who had Neg, Trace, 1+, 2+, and 3+ levels at Screening, Day 14, and Day 35. If a category has not been reported for a specific parameter, then no participants were measured in that category.
Time Frame
Screening (SCR), Day 14, and 35
Title
Mean Urine Specific Gravity Values at Screening, Day 14, and Day 35
Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Time Frame
Screening (SCR), Day 14, and Day 35
Title
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Days 0, 7, 14, 21, and 35
Description
Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Days 0, 7, 14, 21, and 35
Title
Change From Baseline in Heart Rate at Days 0, 7, 14, 21, and 35
Description
Heart rate is defined as the number of heartbeats per unit of time. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Days 0, 7, 14, 21, and 35
Title
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Screening and Day 35
Description
The number of participants with normal, abnormal - clinically significant (CS), and abnormal - not clinically significant (NCS) ECG findings, as well as the number of participants with no results (NR), at Screening and Day 35 are presented. Findings were determined to be normal, abnormal CS, and NCS by the investigator.
Time Frame
Screening (SCR) and Day 35
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who are planning to undergo hematopoietic stem cell transplantation, except cord blood transplantation.
Patients aged from 1 and above to under 65 at the time of informed consent.
Patients who can submit their voluntary written informed consent if they are 12 years old and over.
Patient is male or female. Male patients must be willing to use adequate contraception during the study. Female patients of childbearing potential must agree to consistently perform any of the contraceptive methods.
QTc <450 msec, or QTc <480 msec in patients with bundle branch block. (values based on either single ECG values or triplicate ECG averaged QTc values)
Liver test (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2x upper limit of normal (ULN); alkaline phosphatase (Al-P)and total bilirubin <=1.5xULN (total bilirubin >1.5xULN is acceptable if direct bilirubin <35%).
Exclusion Criteria:
Patients with a history of HSCT.
Patients who are judged to be in the following condition by the investigator (or subinvestigator): the clinical severity of malabsorption syndrome, vomiting, mucositis or other gastrointestinal dysfunction is so serious that orally administered VACV can not be absorbed.
Patients who have known nucleoside analogs hypersensitivity.
Patients who have a concurrent or past history of renal function disorder (serum creatinine >=1.5x ULN).
Patients who have serious complication (eg, other malignant tumours, cardiac disorder, juvenile diabetes).
Patients who are currently treated with the prohibited concomitant drugs.
Patients with evidence of chronic hepatitis B or C.
Patients with AIDS or patients infected with HIV.
Patients who were given other trial products within 30 days before initiation of administration of this trial product or those who intend to participate in other clinical trials.
Patients who are pregnant or probably pregnant.
Patients who can not follow the protocol because of psychological, family, social or geological reasons.
Patients are not allowed to participate in this clinical trial if the investigator (or subinvestigator) judges that their participation is inappropriate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
446-8602
Country
Japan
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
453-8511
Country
Japan
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
GSK Investigational Site
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
GSK Investigational Site
City
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
GSK Investigational Site
City
Hyogo
ZIP/Postal Code
654-0081
Country
Japan
Facility Name
GSK Investigational Site
City
Kagoshima
ZIP/Postal Code
890-8520
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
259-1143
Country
Japan
Facility Name
GSK Investigational Site
City
Osaka
ZIP/Postal Code
594-1101
Country
Japan
Facility Name
GSK Investigational Site
City
Saitama
ZIP/Postal Code
339-8551
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
162-8655
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
116100
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
116100
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
116100
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
116100
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Valaciclovir Hydrochloride Phase III for Hematopoietic Stem Cell Transplantation Patients
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